Cell Dynamics   
 
 Cells are probably the ultimate, most-complex dynamically-self-assembling systems and, as such, they naturally fall into our group's sphere of interest. Here, we are particularly interested in the self-assembly and dynamics of cell components responsible for cell motility. The long-term objective of this work ??under the auspices of NIH/NCI and the Pew Foundation -- is to understand the relationship between directional cell motility and cancer metastasis and to apply this understanding to the discovery of new anti-metastatic therapeutics. To achieve these goals, we combine cell biology with nano/micropatterning techniques and prepare collections of "designer cells" of identical geometries (Nature Methods, 2005). Under such well-defined experimental conditions, it is possible to (i) deconstruct the major components of the cell's "motility machinery" (microtubules, actin stress fibers, focal adhesions) both in space and in time and (ii) study their functioning in populations of live cells of minimal heterogeneity (see a movie of a triangular cell below). Furthermore, by applying the tools of statistical physics to ensembles of identical cells, we are able to elucidate the dynamics of the processes governing cytoskeletal self-organization and cell motility. The synergy between experiments and theory underlies development of new quantitative assays for screening molecules that inhibit cell motility, and is important for the rational design of anti-metastatic drugs (Acct. Chem. Res. 2002).

 

In addition to controlling cell geometry, we also look at how cells migrate through appropriately engineered microenvironments and how they react to geometrical cues. This research (cf. Soft Matter 2007) has already yielded some quite counterintuitive biological insights (would you guess that some cells move more rapidly through more narrow capillaries?) and has enabled development of "ratchet" microsystems that can actually guide cell motions by virtue of geometry alone. The second of the movies below shows one such ratchet that biases otherwise random cell motions in the direction of the pointed edges of the microtriangles. As you might have guessed, the micro-ratchets are very neat tools for sorting out metastatic (motile) from non-metastatic (non-motile) cells. Stay tuned for a series of upcoming papers on this exciting topic.

 

 

 

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